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Examining the role of Rac1 in tumor angiogenesis and growth: a clinically relevant RNAi-mediated approach

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Abstract

Angiogenesis, the sprouting of new blood vessels from the pre-existing vasculature, is a well established target in anti-cancer therapy. It is thought that the Rho GTPase Rac1 is required during vascular endothelial growth factor (VEGF)-mediated angiogenesis. In the present study, we have used a clinically relevant RNA interference approach to silence Rac1 expression. Human umbilical vein endothelial cells were transiently transfected with non-specific control siRNA (siNS) or Rac1 siRNA (siRac1) using electroporation or Lipofectamine 2000. Functional assays with transfected endothelial cells were performed to determine the effect of Rac1 knockdown on angiogenesis in vitro. Silencing of Rac1 inhibited VEGF-mediated tube formation, cell migration, invasion and proliferation. In addition, treatment with Rac1 siRNA inhibited angiogenesis in an in vivo Matrigel plug assay. Intratumoral injections of siRac1 almost completely inhibited the growth of grafted Neuro2a tumors and reduced tumor angiogenesis. Together, these data indicate that Rac1 is an important regulator of VEGF-mediated angiogenesis. Knockdown of Rac1 may represent an attractive approach to inhibit tumor angiogenesis and growth.

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Acknowledgments

Funding is acknowledged from Science Foundation Ireland in the context of the Molecular Therapeutics for Cancer Ireland, Strategic Research Cluster. We further acknowledge funding received from the EU Marie Curie Industry Academia Pathways and Partnership program in the context of the ‘AngioTox’ initiative.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands

    P. Vader, R. van der Meel, M. H. A. M. Fens, E. Pieters, K. J. Wilschut, G. Storm & R. M. Schiffelers

  2. Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research at North Shore-LIJ, 350 Community Drive, Manhasset, NY, 11030, USA

    M. H. Symons

  3. UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland

    W. M. Gallagher

  4. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Reservoir House, Sandyford Industrial Estate, Ballymoss Road, Dublin 18, Ireland

    M. Jarzabek & A. T. Byrne

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  1. P. Vader
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  2. R. van der Meel
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  3. M. H. Symons
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  6. K. J. Wilschut
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  10. R. M. Schiffelers
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  11. A. T. Byrne
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Corresponding author

Correspondence to A. T. Byrne.

Additional information

P. Vader and R. van der Meel contributed equally to this work.

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Vader, P., van der Meel, R., Symons, M.H. et al. Examining the role of Rac1 in tumor angiogenesis and growth: a clinically relevant RNAi-mediated approach. Angiogenesis 14, 457–466 (2011). https://doi.org/10.1007/s10456-011-9229-x

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  • DOI: https://doi.org/10.1007/s10456-011-9229-x

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